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Magnetic susceptibility source separation (χ-separation), an advanced quantitative susceptibility mapping (QSM) method, enables the separate estimation of paramagnetic and diamagnetic susceptibility source distributions in the brain. Similar to QSM, it requires solving the ill-conditioned problem of dipole inversion, suffering from so-called streaking artifacts. Additionally, the method utilizes reversible transverse relaxation ( R2'=R2*-R2$$ {R}_2^{\prime }={R}_2^{\ast }-{R}_2 $$ ) to complement frequency shift information for estimating susceptibility source concentrations, requiring time-consuming data acquisition for R2$$ {R}_2 $$ (e.g., multi-echo spin-echo) in addition to multi-echo GRE data for R2*$$ {R}_2^{\ast } $$ . To address these challenges, we develop a new deep learning network, χ-sepnet, and propose two deep learning-based susceptibility source separation pipelines, χ-sepnet- R2'$$ {R}_2^{\prime } $$ for inputs with multi-echo GRE and multi-echo spin-echo (or turbo spin-echo) and χ-sepnet- R2*$$ {R}_2^{\ast } $$ for input with multi-echo GRE only. The neural network is trained using multiple head orientation data that provide streaking artifact-free labels, generating high-quality χ-separation maps. The evaluation of the pipelines encompasses both qualitative and quantitative assessments in healthy subjects, and visual inspection of lesion characteristics in multiple sclerosis patients. The susceptibility source-separated maps of the proposed pipelines delineate detailed brain structures with substantially reduced artifacts compared to those from the conventional regularization-based reconstruction methods. In quantitative analysis, χ-sepnet- R2'$$ {R}_2^{\prime } $$ achieves the best outcomes followed by χ-sepnet- R2*$$ {R}_2^{\ast } $$ , outperforming the conventional methods. When the lesions of multiple sclerosis patients are classified into subtypes, most lesions are identified as the same subtype in the maps from χ-sepnet- R2'$$ {R}_2^{\prime } $$ and χ-sepnet- R2*$$ {R}_2^{\ast } $$ (paramagnetic susceptibility: 99.6% and diamagnetic susceptibility: 98.4%; both out of 250 lesions). The χ-sepnet- R2*$$ {R}_2^{\ast } $$ pipeline, which only requires multi-echo GRE data, has demonstrated its potential to offer broad clinical and scientific applications, although further evaluations for various diseases and pathological conditions are necessary.

BACKGROUND AND OBJECTIVES: Culturally diverse informal caregivers of community-dwelling persons with dementia face challenges in accessing dementia care resources due to language barriers and cultural stigmas surrounding dementia. This study presents the perceived intervention experiences of a home-based approach which considers the cultural and linguistic needs of diverse family caregivers in dementia care. The intervention model includes home visits by trained bilingual, non-licensed community health workers (CHWs) whose cultural histories and understandings reflect that of the caregivers. The purpose of the present study was to understand family caregivers experience in caregiving and their feedback on the intervention, which includes caregiver support through education and skill development. METHODS: The present study thematically analyzed qualitative data from exit interviews with caregivers who participated in a CHW-led, 12-week home visit-based intervention program. RESULTS: Among 57 caregivers (mean age = 63.5, SD = 14.3) who participated in the 3-month home-visit intervention and completed the exit interviews, 33% were Korean Americans, 28% Vietnamese Americans, 21% non-Hispanic Whites, and 17.5% Latino/Hispanic. The majority were females (81%) and spouses (51%). Main themes include, (a) Individual Level: Improvements in Caregiving Self-efficacy and Self-care Awareness, (b) Relational Level: Enhanced Communications and Relationships with Persons with Dementia, and (c) Community Level: Connection and Access to Community Resources and Support. CONCLUSION: Interview data show that the culturally and linguistically tailored program supported diverse caregivers by increasing self-care awareness, improving knowledge about dementia and dementia care, strengthening communication skills, and facilitating access to community resources. Strong rapport between CHWs and caregivers enhanced the effectiveness of the intervention. Future approaches can focus on supporting caregivers with especially limited resources.

Until now, Hippo pathway-mediated nucleocytoplasmic translocation has been considered the primary mechanism by which yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional coactivators regulate cell proliferation and differentiation via transcriptional enhanced associate domain (TEAD)-mediated target gene expression. In this study, however, we found that TAZ, but not YAP, is associated with the Golgi apparatus in macrophages activated via Toll-like receptor ligands during the resolution phase of inflammation. Golgi-associated TAZ enhanced vesicle trafficking and secretion of proinflammatory cytokines in M1 macrophage independent of the Hippo pathway. Depletion of TAZ in tumor-associated macrophages promoted tumor growth by suppressing the recruitment of tumor-infiltrating lymphocytes. Moreover, in a diet-induced metabolic dysfunction-associated steatohepatitis model, macrophage-specific deletion of TAZ ameliorated liver inflammation and hepatic fibrosis. Thus, targeted therapies being developed against YAP/TAZ-TEAD are ineffective in macrophages. Together, our results introduce Golgi-associated TAZ as a potential molecular target for therapeutic intervention to treat tumor progression and chronic inflammatory diseases.

Doxorubicin is a highly effective anticancer agent, but its clinical use is restricted by severe side effects, including atherosclerosis and cardiomyopathy. These complications are partly attributed to doxorubicins ability to induce endothelial-to-mesenchymal transition (EndMT) in vascular endothelial cells, a critical process in the initiation and progression of atherosclerosis and cardiomyopathy. GV1001, a multifunctional peptide with anti-inflammatory, anti-cancer, antioxidant, and anti-Alzheimers properties, has demonstrated inhibition of EndMT. We investigated whether GV1001 could counteract doxorubicin-induced EndMT in endothelial cells and prevent atherosclerosis in a mouse model. The results revealed that GV1001 significantly suppressed EndMT induced by doxorubicin, likely through its protective effects on mitochondria. By mitigating mitochondrial damage, GV1001 reduced the accumulation of mitochondrial and cellular reactive oxygen species (ROS), repressed the activation of nuclear factor kappa B (NF-κB), and reduced the production of proinflammatory cytokines in endothelial cells. Additionally, GV1001 reduced systemic and vascular inflammation, lipid accumulation, and monocyte/macrophage infiltration within arterial walls in mice. In conclusion, GV1001 appears to prevent doxorubicin-induced atherosclerosis by safeguarding vascular endothelial cells from mitochondrial dysfunction, inflammation, and phenotypic changes. These findings suggest the potential of GV1001 as a therapeutic agent to mitigate the long-term cardiovascular side effects associated with doxorubicin treatment in humans.

Studies on the gastric microbiota associated with gastric precancerous lesions remain limited. This study aimed to profile the gastric mucosal microbiota in patients with Helicobacter pylori-negative precancerous lesions. Gastric mucosal samples were obtained from 67 H. pylori-negative patients, including those with chronic gastritis (CG), intestinal metaplasia (IM), and dysplasia. The V3-V4 region of the 16S rRNA gene was sequenced and analyzed. No significant difference was observed in the alpha or beta diversity of the gastric microbiota among the groups. However, a taxonomic analysis revealed a significant enrichment of Lautropia mirabilis and the depletion of Limosilactobacillus reuteri, Solobacxterium moorei, Haemophilus haemolyticus, and Duncaniella dubosii in the IM and dysplasia groups compared to those in the CG group. Prevotella jejuni and the genus Parvimonas were enriched in the IM group. A predictive functional analysis revealed enrichment of the ornithine degradation pathway in the IM and dysplasia groups, suggesting its role in persistent gastric mucosal inflammation associated with gastric precancerous lesions. The gastric microbiota associated with H. pylori-negative gastric precancerous lesions showed an increased abundance of oral microbes linked to gastric cancer and a reduction in anti-inflammatory bacteria. These alterations might contribute to chronic gastric mucosal inflammation, promoting carcinogenesis in the absence of H. pylori infection.

Colloidal nanocrystals inherently undergo structural changes during chemical reactions. The robust structure-property relationships, originating from their nanoscale dimensions, underscore the significance of comprehending the dynamic structural behavior of nanocrystals in reactive chemical media. Moreover, the complexity and heterogeneity inherent in their atomic structures require tracking of structural transitions in individual nanocrystals at three-dimensional (3D) atomic resolution. In this study, we introduce the method of time-resolved Brownian tomography to investigate the temporal evolution of the 3D atomic structures of individual nanocrystals in solution. The methodology is applied to examine the atomic-level structural transformations of Pt nanocrystals during oxidative etching. The time-resolved 3D atomic maps reveal the structural evolution of dissolving Pt nanocrystals, transitioning from a crystalline to a disordered structure. Our study demonstrates the emergence of a phase at the nanometer length scale that has received less attention in bulk thermodynamics.

Disordered rocksalt cathodes exhibit high specific capacities and high energy density; however, their low electronic conductivity poses a great challenge. Herein, we explored an aqueous-solution-based synthesis route that involves controlling the surface charges of Li1.2Mn0.6Ti0.2O1.8F0.2 (LMTOF) to be anchored by a few-layer reduced graphene oxide (rGO) for the first time. The uniform rGO wrapping on the surface of the LMTOF particles is achieved by electrostatic attraction between the negatively charged rGO and positively charged LMTOF particles. Although the initial specific capacity of rGO-LMTOF composite increased by 58 % compared to the pristine LMTOF, the composite experienced a severe capacity fade over cycling. The synthesis process in an aqueous medium resulted in Li+/H+ exchange and TM dissolution as evidenced from inductively coupled plasmon analysis and X-ray diffraction analysis. Therefore, this work suggests the search for alternative media or conditions for the synthesis of carbon-disordered rock salt cathode composite.

The immune system continuously interacts with tumors, possibly leading to systemic alterations in circulating immune cells. However, the potential of these cancer-associated changes for diagnostic purposes remains poorly explored. To investigate this, we conducted a comprehensive flow cytometric analysis of 452 peripheral blood mononuclear cell (PBMC) samples from 206 non-small-cell lung cancer (NSCLC) patients, 100 small-cell lung cancer (SCLC) patients, 94 healthy individuals, and 52 benign lung disease (BLD) patients. We focused specifically on circulating T cells, given their close interaction with tumors, and initially assessed 93 T-cell features from the flow cytometric analysis. Using a feature selection protocol, we identified five T-cell features in peripheral blood with strong diagnostic relevance. Notably, while individual alterations in these features lacked cancer specificity, simultaneous alterations were uniquely indicative of lung cancer. To comprehensively analyze these features, we developed a scoring model, IMmunoPhenotypic Analysis for Cancer deTection (IMPACT). Comprehensive analysis using the five features (IMPACT-5) demonstrated high cancer specificity and biomarker efficacy, as evidenced by the high area under the receiver operating characteristic curve values for lung cancer patients (0.9187, 0.9277, and 0.9363 for stage I NSCLC, stage IV NSCLC, and SCLC patients, respectively), in stark contrast to BLD patients (0.5212). These findings suggest that comprehensive analysis of cancer-associated changes in circulating T cells can effectively detect lung cancer from its early stages, proposing immunophenotypic analysis of circulating T cells as an innovative liquid biopsy-based diagnostic biomarker.

To achieve the commercialization of two-dimensional (2D) semiconductors, the identification of an appropriate combination of 2D semiconductors and three-dimensional (3D) metals is crucial. Furthermore, understanding the van der Waals (vdW) interactions between these materials in thin-film semiconductor processes is essential. Optimizing these interactions requires precise control over the properties of the vdW interface through specific pre- or post-treatment methods. This study utilizes Se-environment annealing as a post-treatment technique, which allows for modification of the vdW gap distance and enhancement of the stability of the interfacial structure through the process of Se intercalation and deintercalation at the 2D-3D interface. The depth of Se intercalation and deintercalation is adjusted by varying the temperature and duration of the postannealing process in an Se environment. This precise control over the process enables the effective metallization of 2D semiconductors. The results indicate that expanding the vdW gap and stabilizing the interface structure through this post-treatment significantly improve the metal contact properties in devices such as field-effect transistors and photovoltaic Schottky diodes by minimizing metal-induced gap states, thus reducing Fermi level pinning. The application of Se intercalation and deintercalation techniques achieves an exceptionally low contact resistance of 773 Ω·μm between p-type WSe2 and Au. Additionally, the integration of doping-free WSe2 complementary metal-oxide-semiconductor (CMOS) circuits using Se-environment annealing and blocking layers is demonstrated, establishing a promising advancement in semiconductor technology.

Different subsets of Alzheimer's disease neuropathologic change (ADNC), including the intriguing set of individuals with severe/widespread amyloid-β (Aβ) plaques but no/mild tau tangles [Aβ-predominant (AP)-ADNC], may have distinct genetic and clinical features. Analysing National Alzheimer's Coordinating Center data, we stratified 1187 participants into AP-ADNC (n = 95), low Braak primary age-related tauopathy (PART; n = 185), typical-ADNC (n = 832) and high-Braak PART (n = 75). AP-ADNC differed in some clinical features and genetic polymorphisms in the APOE, SNX1, WNT3/MAPT and IGH genes. We conclude that AP-ADNC differs from classical ADNC with implications for in vivo studies.

BACKGROUND: Disorders of gut-brain interaction (DGBI) predominate in women, but little is known about sex differences in menses-related or menopause symptoms. METHODS: Using data from the Rome Foundation Global Epidemiology Survey, we assessed Rome IV DGBI symptoms in individuals in 26 countries who met criteria for ≥ 1 of 5 DGBI: irritable bowel syndrome (IBS), functional dyspepsia (FD), functional constipation (FC), functional diarrhea (FDr), or functional bloating (FB). Participants included pre- and post-menopausal women with DGBI and age-matched men. Odds ratios estimated sex and age differences for symptom by sex or pre- vs. post-menopause in logistic regression; standardized mean difference (SMD) provided effect sizes. KEY RESULTS: 14,570 participants met criteria for ≥ 1 of the 5 DGBI. Women exceeded men in most symptoms. In FD, women stopped eating due to early satiety more than men (11.1 vs. 8.9 days/month, SMD 0.21). Symptoms were generally increased in premenopausal women and younger men compared to older counterparts; however, only premenopausal IBS, FD, and FC women reported increased constipation-associated symptoms. Compared to premenopausal women, postmenopausal women had increased accidental stool leakage in IBS and FDr, and increased digital manual maneuvers in FC (18% vs. 25% frequency, SMD -0.25). IBS and FD had the most menses-associated symptoms. CONCLUSIONS AND INFERENCES: Women had higher symptom frequency across the 5 DGBI compared to men. Our findings suggest that premenopausal women have greater visceral perception than postmenopausal women, although increased outlet symptoms in postmenopausal women indicate greater anorectal/pelvic dysfunction. While age alone has some influence on symptoms, female sex hormones may also increase visceral perception.

BACKGROUND: Children from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health. METHODS: We conducted a retrospective cohort study of individuals

Planted cover crops and naturally occurring resident vegetation in orchards and agricultural fields belong to multiple functional groups which differ in traits, growth dynamics, and ability to influence soil health and biology. These different vegetation mixes may influence soil food webs and ecosystems over a growing season as well as regulating nutrient cycling outcomes. This study characterized soil organisms and nutrients as well as physical and chemical indicators of soil health in an almond orchard with three vegetation mixes: winter resident vegetation (dominated by Vicia, Malva, and Hordeum weedy species), and two cover crops mixes, one functionally diverse (brassica, legume, cereals) and one functionally uniform (brassicas), all of which had been implemented for four years. While physical soil health indicators differed seasonally, only biological indicators differed among the vegetation. During the winter and early spring growth period, both cover crop mixes increased microbial biomass nitrogen compared to resident vegetation, while the uniform mix supported greater numbers of nematodes overall, regardless of trophic group. The diverse cover crop mix supported more complex nematode food webs, as measured by the Structure Footprint, while nematode communities overall were primarily influenced by cover crop biomass and microbial biomass nitrogen. Soil nutrients increased after vegetation termination by flail mowing in all treatments, and the resident vegetation had the largest increase in dissolved organic carbon between the Cover and Post-Cover time points. Nematode indicators of food web composition and function decreased after termination, including the Structure Index, Fungal Footprint and Bacterivore Footprint. In contrast, the relative abundance of herbivores increased over time and, at the Post-Cover time point, both the diverse mix and the uniform mix had a higher proportion of root herbivores than resident vegetation, although these were primarily in the genus Tylenchorhynchus and not considered economically damaging. Increased processing of resources through generalist root herbivore nematodes may have been due to nematodes feeding on the cover crops themselves or on almond roots that foraged into soils with more nutrients. These results suggest that cover cropping can influence soil food webs on multiple fronts including root herbivores and predators. Greater knowledge of how cover crops influence soil health and for how long, during a season, will allow for the more efficient use of cover crops in Mediterranean systems.

BackgroundChildren from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health.MethodsWe conducted a retrospective cohort study of individuals

PURPOSE: It is uncertain whether, and to what extent, hormonal contraceptives increase breast cancer (BC) risk for germline BRCA1 or BRCA2 mutation carriers. METHODS: Using pooled observational data from four prospective cohort studies, associations between hormonal contraceptive use and BC risk for unaffected female BRCA1 and BRCA2 mutation carriers were assessed using Cox regression. RESULTS: Of 3,882 BRCA1 and 1,509 BRCA2 mutation carriers, 53% and 71%, respectively, had ever used hormonal contraceptives for at least 1 year (median cumulative duration of use, 4.8 and 5.7 years, respectively). Overall, 488 BRCA1 and 191 BRCA2 mutation carriers developed BC during median follow-up of 5.9 and 5.6 years, respectively. Although for BRCA1 mutation carriers, neither current nor past use of hormonal contraceptives for at least 1 year was statistically significantly associated with BC risk (hazard ratio [HR], 1.40 [95% CI, 0.94 to 2.08], P = .10 for current use; 1.16 [0.80 to 1.69], P = .4, 1.40 [0.99 to 1.97], P = .05, and 1.27 [0.98 to 1.63], P = .07 for past use 1-5, 6-10, and >10 years before, respectively), ever use was associated with increased risk (HR, 1.29 [95% CI, 1.04 to 1.60], P = .02). Furthermore, BC risk increased with longer cumulative duration of use, with an estimated proportional increase in risk of 3% (1%-5%, P = .002) for each additional year of use. For BRCA2 mutation carriers, there was no evidence that current or ever use was associated with increased BC risk (HR, 0.70 [95% CI, 0.33 to 1.47], P = .3 and 1.07 [0.73 to 1.57], P = .7, respectively). CONCLUSION: Hormonal contraceptives were associated with increased BC risk for BRCA1 mutation carriers, especially if used for longer durations. Decisions about their use in women with BRCA1 mutations should carefully weigh the risks and benefits for each individual.

OBJECTIVES: There is growing interest in assessing patient quality of life (QOL) following treatment of sinonasal tumors, including inverted papilloma (IP). We aimed to elucidate the natural history of postoperative QOL outcomes in IP patients treated with surgery. METHODS: Cases of sinonasal IP treated surgically at 4 tertiary academic rhinology centers were retrospectively reviewed. SNOT-22 scores were used to evaluate QOL preoperatively and postoperatively (1, 3, 6, 12 months). Repeated-measures ANOVA assessed for differences in mean scores over time. Linear regression identified factors associated with QOL longitudinally. RESULTS: 373 patients were analyzed. Mean preoperative SNOT-22 score was 20.6 ± 20.4, which decreased to 16.3 ± 18.8 (p = 0.041) and 11.8 ± 15.0 (p  0.05). When analyzed by SNOT-22 subdomains, nasal, sleep, and otologic/facial subdomain scores (all p  0.05). CONCLUSIONS: QOL outcomes related to IP resection are largely driven by nasal, sleep, and otologic/facial subdomains, though patients appear to experience enduring improvement as early as 3 months postoperatively. Recurrent disease is a major driver of negative QOL. LEVEL OF EVIDENCE: 4 Laryngoscope, 135:579-585, 2025.

Interest in animal cell-based meat (ACBM) as an environmentally conscious replacement for livestock production has been increasing; however, a life cycle assessment (LCA) for the existing production methods of ACBM has not been conducted. Currently, ACBM products are being produced at a small scale, but ACBM companies are intending to scale-up production. Updated findings from recent technoeconomic assessments (TEAs) of ACBM were utilized to perform an LCA of near-term ACBM production. A scenario analysis was conducted utilizing the metabolic requirements examined in the TEAs of ACBM, and a purification factor was utilized to account for growth medium component processing. The results indicate that the environmental impact of near-term ACBM production has the potential to be significantly higher than beef if a highly refined growth medium is utilized for ACBM production. This study highlights the need to develop a sustainable animal cell growth medium that is optimized for high-density animal cell proliferation for ACBM to generate positive economic and environmental benefits.

Precise and rapid disease detection is critical for controlling infectious diseases like COVID-19. Current technologies struggle to simultaneously identify viral RNAs and host immune antibodies due to limited integration of sample preparation and detection. Here, we present acoustofluidic integrated molecular diagnostics (AIMDx) on a chip, a platform enabling high-speed, sensitive detection of viral immunoglobulins [immunoglobulin A (IgA), IgG, and IgM] and nucleic acids. AIMDx uses acoustic vortexes and Gor'kov potential wells at a 1/10,000 subwavelength scale for concurrent isolation of viruses and antibodies while excluding cells, bacteria, and large (>200 nanometers) vesicles from saliva samples. The chip facilitates on-chip viral RNA enrichment, lysis in 2 minutes, and detection via transcription loop-mediated isothermal amplification, alongside electrochemical sensing of antibodies, including mucin-masked IgA. AIMDx achieved nearly 100% recovery of viruses and antibodies, a 32-fold RNA detection improvement, and an immunity marker sensitivity of 15.6 picograms per milliliter. This breakthrough provides a transformative tool for multiplex diagnostics, enhancing early infectious disease detection.

Introduction: Tics in children are commonly diagnosed and not usually a cause for concern. Rarely, they may present as a symptom of underlying intracranial pathology.Case Report: We describe an adolescent with sudden-onset tics following a fall who presented to the emergency department and was diagnosed with an arteriovenous malformation with parenchymal hemorrhage. He underwent a successful embolization, after which his tics resolved.Conclusion: When evaluating a patient with tics, an atypical history or abnormal physical exam findings should raise suspicion for possible secondary etiologies, including arteriovenous malformation and stroke.

Cardiac masses are complex clinical conditions that frequently pose diagnostic challenges in cardiology practice. These masses can form within heart chambers or near the pericardium and are generally categorized as either non-neoplastic or neoplastic. These latter are further classified into benign and malignant (primary and secondary or metastatic). Diagnosing these conditions often requires a multiparametric approach that includes both clinical features, such as the patients and associated clinical conditions, and multimodality imaging. However, histological examination of the resected specimen is often necessary to ascertain the nature of the mass. Given their heterogeneity and the rarity of many cardiac masses, there are no guidelines or consensus on the best diagnostic approach. Modern imaging protocols must be tailored to the specific clinical issues and patient characteristics, given the rapid advancements in technology. Thus, it is imperative to use a multimodality approach, combining different imaging techniques and multidisciplinary teamwork. Hereby, we propose a practical algorithm for evaluating cardiac lesions using a step-by-step implementation of multimodal imaging. Ultimately, the goal is to tailor the most suitable imaging technique to the patients needs.

Multivalent-ion batteries offer an alternative to Li-based technologies, with the potential for greater sustainability, improved safety, and higher energy density, primarily due to their rechargeable system featuring a passivating metal anode. Although a system based on the Ca2+/Ca couple is particularly attractive given the low electrochemical plating potential of Ca2+, the remaining challenge for a viable rechargeable Ca battery is to identify Ca cathodes with fast ion transport. In this work, a high-throughput computational pipeline is adapted to (1) discover novel Ca cathodes in a largely unexplored space of empty intercalation hosts and (2) develop material design rules for Ca-ion mobility. One candidate from the screening, W2O3(PO4)2, is confirmed to have a low Nudged Elastic Band (NEB) barrier of 168 meV within a one-dimensional (1D) ion percolation topology. This candidate is subsequently synthesized and electrochemically tested, achieving reversible Ca cycling with a capacity of 25 mA h/g. To further accelerate the screening for promising Ca intercalation electrodes, machine learning (ML) Random Forest (RF) and Extreme Gradient Boosting (XGB) classification models are created with local environment descriptors based on a large, structurally and chemically diverse dataset of minimum energy pathways, spanning over 5,000 density functional theory (DFT) site energy calculations. Accuracies of 92% are achieved, material design metrics are quantified, ML force-fields are leveraged in an accelerated iteration of the screening, and a total of 27 novel Ca cathode materials are highlighted for further investigation.

Objective: The objective of this study was to assess clinical decision-making associated with the use of a multi-analyte blood biomarker (BBM) test among patients presenting with signs or symptoms of mild cognitive impairment or dementia. Methods: The Quality Improvement PrecivityAD2 (QUIP II) Clinician Survey (NCT06025877) study evaluated the clinical utility of the PrecivityAD2™ blood test in a prospective, single cohort of 203 patients presenting with symptoms of Alzheimers disease (AD) or other causes of cognitive decline across 12 memory specialists. The PrecivityAD2 blood test (C2N Diagnostics, St. Louis, MO) combines the plasma Aβ42/Aβ40 ratio and the p-tau217/np-tau217 ratio (%p-tau217) measurements in a statistical algorithm to yield an Amyloid Probability Score 2 (APS2) that informs on the likelihood of brain amyloid plaques. After receiving the BBM test results, clinicians completed surveys on management strategies for each patient. Results: Patients had a median age of 74, 53% were female, and 28% were traditionally under-represented in Black, Hispanic, and Asian groups. The composite primary endpoint, defined as a change in AD diagnostic certainty, drug therapy, or additional brain amyloid evaluation pre- and post-BBM testing, was 75% (p < 0.0001 versus the pre-specified threshold of 20% clinically meaningful change). Anti-AD medication orders decreased among negative APS2 patients and increased among positive APS2 patients (p < 0.0001). Additional brain amyloid testing decreased among negative APS2 patients (p < 0.0001). Conclusions: This blood biomarker test can help memory specialists guide patients to anti-AD therapies as well as rule out AD to allow for other diagnostic considerations.

Here, we present a protocol for using Myotally, a user-friendly software for fast, automated quantification of muscle fiber size, number, and central nucleation from immunofluorescent stains of mouse skeletal muscle cross-sections. We describe steps for installing the software, preparing compatible images, finding the file path, and selecting key parameters like image quality and size limits. We also detail optional features, such as measuring mean fluorescence. By automating these traditionally labor-intensive processes, Myotally improves research efficiency and data consistency.

Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis. Consequently, lipochondrocytes grew uniform lipid droplets that resisted systemic lipid surges and did not enlarge upon obesity. Lipochondrocytes also lacked lipid mobilization factors, which enabled exceptional vacuole stability and protected cartilage from shrinking upon starvation. Lipid droplets modulated lipocartilage biomechanics by decreasing the tissue's stiffness, strength, and resilience. Lipochondrocytes were found in multiple mammals, including humans, but not in nonmammalian tetrapods. Thus, analogous to bubble wrap, superstable lipid vacuoles confer skeletal tissue with cartilage-like properties without "packing foam-like" extracellular matrix.

Light-driven reduction of CO2 into chemicals using a photoelectrochemical (PEC) approach is considered as a promising way to meet the carbon neutral target. The very top surface of the photoelectrode and semiconductor/electrolyte interface plays a pivotal role in defining the performance for PEC CO2 reduction. However, such impact remains poorly understood. Here, we report an electrodeposition-annealing route for tailoring surface composition of ZnTe photocathodes. Our work demonstrates that a Zn-rich surface on the ZnTe photocathode is essential to impact the CO2 reduction activity and selectivity. In particular, the Zn-rich surface not only facilitated the interfacial charge carrier transfer, but also acted as electrocatalyst for boosting carbon product selectivity and suppressing the hydrogen evolution reaction. This work provides a new avenue to optimize the photocathode, as well as improvement of the CO2RR performance.

BackgroundCancer survivors are at increased risk for cardiometabolic comorbidities following cancer treatment, which may be further exacerbated by cannabis and alcohol use. We aimed to examine the direct relationships of cannabis, alcohol, and the co-use of both substances with cardiometabolic risk factors and to explore disparities by race/ethnicity and sex.MethodsCross-sectional data were extracted from adult cancer survivors in the "All of Us" from 2018 to 2022. Cannabis use was defined as occasional or frequent/regular cannabis use (vs. never) in the past 3 months and hazardous alcohol intake (AUDIT-C >3 for females; AUDIT-C >4 for males) versus nonhazardous in the past year, respectively. Co-use was defined as participants who engaged in regular cannabis and hazardous alcohol intake. We identified binary cardiovascular, immune, and metabolic system biomarkers, with high values defined by clinically established cutoffs or >75th percentile. We used multivariable logistic regression adjusting for sociodemographic and clinical factors.ResultsIn our sample (N = 7,054), 7.6% were Hispanic, 6.2% were Black, and 86.2% were White cancer survivors. Less than 5% of Hispanic and White survivors reported substance co-use compared with 7% of Black survivors. Compared with never-users, co-users were 1.58 (95% confidence interval, 1.14-2.19) more likely to have high blood pressure. No significant associations were found between co-use and immune biomarkers or sex differences.ConclusionsCo-use of cannabis and hazardous alcohol may worsen high blood pressure in survivors, who are at higher risk for cardiometabolic comorbidities.ImpactThe study investigates substance use and cardiometabolic biomarkers, urging much research on their effects on cancer survivors.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma). Overexpression of ZIC1 suppresses the growth of group 3 medulloblastoma models, whereas it promotes the proliferation of SHH medulloblastoma precursor cells. SHH medulloblastoma ZIC1 mutants show increased activity versus wild-type ZIC1, whereas G4 medulloblastoma ZIC1 mutants exhibit LOF phenotypes. Distinct ZIC1 mutations affect cells of the rhombic lip in diametrically opposed ways, suggesting that ZIC1 is a critical developmental transcriptional regulator in both the normal and transformed rhombic lip and identifying ZIC1 as an exquisitely context-dependent driver gene in medulloblastoma.

Many contemporary imaging systems seek tunable focusing components with minimal form factors and versatile functionalities; however, existing solutions are typically limited in size, efficiency, and tuning speed. Here, low-loss all-dielectric metasurfaces integrated with liquid crystals (LCs) are used to demonstrate highly compact multifunctional zoom components. The phase profiles imparted by the metalens are modulated in real time by means of field-dependent LCs, enabling electrically driven continuous focal length variation and active bifocal imaging with low applied voltages (

OBJECTIVE: To assess changes in noncontrast magnetic resonance imaging (MRI)-based biomarkers after upper extremity lymphedema surgery. METHODS: We retrospectively identified secondary upper extremity lymphedema patients who underwent vascularized lymph node transplant (VLNT), debulking lipectomy, or VLNT with a prior debulking (performed separately). All patients with both preoperative and postoperative MRIs were compared. An MRI-based edema scoring system was used: 0 (no edema), 1 (

Background and objectivesHuman trafficking (HT) is a public health issue, with adolescents disproportionately at risk for reasons spanning multiple biopsychosocial domains. We explored youth HT survivors' healthcare barriers, experiences, and needs.MethodsIn this qualitative multi-methods study, 24 participants (≤26 years old) with HT experience receiving services from non-profit organizations in San Diego, California completed an electronic survey and were invited to participate in online interviews. Thematic analysis for interview responses was performed using constant comparative methodology. Authors created codes and connections between codes, and refined findings by discussion.ResultsAll participants endorsed labor trafficking, 96% endorsed sex trafficking and 46% reported seeing a health care professional (HCP) while exploited. Nine survey respondents completed follow-up interviews: 100% endorsed labor and sex trafficking and 44% seeing a HCP. Interview participants' barriers to presenting to healthcare and receiving needed help were categorized into patient-focused - lack of awareness of exploitation and medical needs, emotional bonds to the trafficker, and misperceptions about their ability to obtain care); vs healthcare system-focused - negative experiences and need for consistency with HCPs, and desire for targeted resources and effective care.ConclusionsBarriers to healthcare for trafficked youth included factors the healthcare system could change versus those that could be reduced with universal patient education. Participants named lack of legal guardian support and proof of insurance as barriers to healthcare access while being exploited. Participants noted conventional mental health interventions for recovery are not appropriate and lack survivor-led guidance; participants offered alternatives about how they would receive effective care.

BackgroundChronic limb-threatening ischemia (CLTI) in patients with chronic kidney disease (CKD) has a high risk of poor outcomes. We aimed to compare the outcomes of lower extremity revascularization in patients with CLTI stratified by CKD severity in patients enrolled in the prospective, randomized Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial.MethodsThe BEST-CLI trial dataset was queried to categorize patients into three groups according to CKD stage. Group A includes non-CKD and CKD stages

Abstract: Research in cultural anthropology and the interdisciplinary field of science and technology studies (STS) has demonstrated that environmental disasters are not only techno-scientifically and socio-politically complex but also epistemically complex -- involving perspectival diversity; multiple, often conflicting forms of evidence; data gaps and disinformation; and role transitions and confusions. Disasters, this research has demonstrated, are highly fraught knowledge problems that nevertheless call for pragmatic response. In this article, we describe an approach to disaster education that stems from this premise, mobilizing an Environmental Injustice Case Study Framework that draws out multiple dimensions of disaster, foregrounding the need for interdisciplinarity while immersing students in the challenges and paradoxes of disaster knowledge production. We offer both an instructional approach and a theoretical perspective on what case study pedagogy in disaster education accomplishes, and can contribute to science education writ large. Our argument is that critical approaches to case study pedagogy can scaffold many kinds of learning in both disaster and science education, helping students integrate diverse kinds of data, analysis, interpretation, and judgment, while building metacognition and epistemic reflexivity.

Chemotherapy treatment-related side effects are common and increase the risk of suboptimal outcomes. Exercise interventions during cancer treatment improve self-reported physical functioning, fatigue, anxiety, and depression, but it is unclear whether these interventions improve important clinical outcomes, such as chemotherapy relative dose intensity. The National Cancer Institute funded the Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO) Consortium to address this knowledge gap. This article describes the mechanisms hypothesized to underpin intervention effects on clinically relevant treatment outcomes, briefly outlines each projects distinct research aims, summarizes the scope and organizational structure of ENICTO, and provides an overview of the integrated common data elements used to pursue research questions collectively. In addition, the article includes a description of consortium-wide activities and broader research community opportunities for collaborative research. Findings from the ENICTO Consortium have the potential to accelerate a paradigm shift in oncology care such that patients with cancer could receive exercise and nutrition programming as the standard of care in tandem with chemotherapy to improve relative dose intensity for a curative outcome.

SGLT2 inhibitors and GLP1 receptor agonists have kidney protective effects. By combining immunostaining-guided laser capture microdissection and RNA sequencing, the study established how the gene expression profile changes in SGLT2-positive proximal tubule cells in response to type 1 Akita diabetes and to pharmacological intervention by SGLT2 inhibition or GLP1R agonism and genetic deletion of SGLT1. The data also indicate genes unresponsive to those treatments that may include new therapeutical candidates.

Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a prospective multicenter cohort of 86 transplant recipients age- and sex-matched with 172 non-transplant controls. We find that transplant recipients have higher nasal SARS-CoV-2 viral abundance and impaired viral clearance, and lower anti-spike IgG levels. In addition, transplant recipients exhibit decreased plasmablasts and transitional B cells, and increased senescent T cells. Blood and nasal transcriptional profiling demonstrate unexpected upregulation of innate immune signaling pathways and increased levels of several proinflammatory serum chemokines. Severe disease in transplant recipients, however, is characterized by a less robust induction of pro-inflammatory genes and chemokines. Together, our study reveals distinct immune features and altered viral dynamics in solid organ transplant recipients.

Chronic hepatitis B remains a substantial global health challenge, impacting approximately 254 million people worldwide. A cure for this condition is yet to be discovered. Early identification and effective treatments coupled with vigilant monitoring can help alleviate associated morbidity and mortality due to potential complications such as liver cirrhosis and hepatocellular carcinoma.

Tumor initiation represents the first step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Capturing this process as it occurs in vivo, however, remains elusive. Here we employ spatiotemporally controlled oncogene activation and tumor suppressor inhibition together with multiomics to unveil the processes underlying oral epithelial progenitor cell reprogramming into tumor initiating cells at single cell resolution. Tumor initiating cells displayed a distinct stem-like state, defined by aberrant proliferative, hypoxic, squamous differentiation, and partial epithelial to mesenchymal invasive gene programs. YAP-mediated tumor initiating cell programs included activation of oncogenic transcriptional networks and mTOR signaling, and recruitment of myeloid cells to the invasive front contributing to tumor infiltration. Tumor initiating cell transcriptional programs are conserved in human head and neck cancer and associated with poor patient survival. These findings illuminate processes underlying cancer initiation at single cell resolution, and identify candidate targets for early cancer detection and prevention.

BACKGROUND: There are few opportunities in undergraduate medical education that provide formal training in engineering and scientific innovation. Institutions have sought to address student-specific career goals through combined degree programs such as the Medical Scientist Training Program and MD/MBA. However, only a small percentage of medical students pursue these additional degrees. Partnerships between medical schools and Medical Technology (MedTech) accelerators may create unique opportunities for medical students to gain real-world experience with scientific innovation and entrepreneurship. METHODS: An internship program was developed by the Keck Translational Biotechnology Association and the West Coast Consortium for Technology & Innovation in Pediatrics (CTIP), a Food and Drug Administration-funded pediatric medical device accelerator. Students and companies applied to participate and were paired based on students interests and experience, and project plans were developed together. An initial orientation provided an overview of the program structure and expectations. Students and mentors met biweekly to address questions or concerns surrounding the progress of their projects. Students gave final project presentations and completed program evaluations. Data from 3 iterations of the program are reported. RESULTS: Student program satisfaction was measured across 5 domains. Students felt that working with CTIP was valuable to their education (mean score = 3.7 of 5.0) and encouraged them to pursue future careers in MedTech (mean score = 4.0 of 5.0). Students provided a few suggestions to improve the program, including more structure, clear expectations around time commitment and deliverables, and stipends for students. Participation in the program grew over time. CONCLUSIONS: The initial iterations of the internship program were well received by students. Several opportunities for improvement were noted. The program grew over time. Partnerships with accelerator programs at medical schools and academic medical centers may provide key real-world opportunities for students to learn about MedTech.

To improve occupant comfort and save energy in buildings, we have developed a closed-loop air conditioning (AC) sensor-controller that predicts occupant thermal sensation from the thermographic measurement of skin temperature distribution and then uses this information to reduce overcooling (cooling-energy overuse that discomforts occupants) by regulating AC output. Taking measures to protect privacy, it combines thermal-infrared (TIR) and color (visible spectrum) cameras with machine vision to measure the skin-surface temperature profile. Since the human thermoregulation system uses skin blood flow to maintain thermoneutrality, the distribution of skin temperature can be used to predict warm, neutral, and cool thermal states. We conducted a series of human-subject thermal-sensation trials in cold-to-hot environments, measuring skin temperatures and recording thermal sensation votes. We then trained random-forest classification machine-learning models (classifiers) to estimate thermal sensation from skin temperatures or skin-temperature differences. The estimated thermal sensation was input to a proportional-integral (PI) control algorithm for the AC, targeting a sensation level between neutral and warm. Our sensor-controller includes a sensor assembly, server software, and client software. The server software orients the cameras and transmits images to the client software, which in turn assesses occupant skin temperature distribution, estimates occupant thermal sensation, and controls AC operation. A demonstration conducted in a conference room in an office building near Houston, TX showed that our system reduced overcooling, decreasing AC load by 42% when the room was occupied while improving occupant comfort (fraction of “comfortable” votes) by 15 percentage points.

We study an Expectation-Maximization (EM) algorithm for estimating product-term regression models with missing data. The study of such problems in the frequentist tradition has thus far been restricted to an EM algorithm method using full numerical integration. However, under most missing data patterns, we show that this problem can be solved analytically, and numerical approximations are only needed under specific conditions. Thus we propose a hybrid EM algorithm, which uses analytic solutions when available and approximate solutions only when needed. The theoretical framework of our algorithm is described herein, along with three empirical experiments using both simulated and real data. We demonstrate that our algorithm provides greater estimation accuracy, exhibits robustness to distributional violations, and confers higher power to detect interaction effects. We conclude with a discussion of extensions and topics of further research.

PurposeCorneal dysmorphologies (CDs) are typically classified as either regressive degenerative corneal dystrophies (CDtrs) or defective growth and differentiation-driven corneal dysplasias (CDyps). Both eye disorders have multifactorial etiologies. While previous work has elucidated many aspects of CDs, such as presenting symptoms, epidemiology, and pathophysiology, the genetic mechanisms remain incompletely understood. The purpose of this study was to analyze phenotype data from 8,707 knockout mouse lines to identify new genes associated with the development of CDs in humans.Methods8,707 knockout mouse lines phenotyped by the International Mouse Phenotyping Consortium were queried for genes associated with statistically significant (P

BackgroundPerivascular spaces (PVS) on brain MRI are surrogates for small parenchymal blood vessels and their perivascular compartment, and may relate to brain health. However, it is unknown whether PVS can predict dementia risk and brain atrophy trajectories in participants without dementia, as longitudinal studies on PVS are scarce and current methods for PVS assessment lack robustness and inter-scanner reproducibility.MethodsWe developed a robust algorithm to automatically assess PVS count and size on clinical MRI, and investigated 1) their relationship with dementia risk and brain atrophy in participants without dementia, 2) their longitudinal evolution, and 3) their potential use as a screening tool in simulated clinical trials. We analysed 46,478 clinical measurements of cognitive functioning and 20,845 brain MRI scans from 10,004 participants (71.1 ± 9.7 years-old, 56.6% women) from three publicly available observational studies on ageing and dementia (the Alzheimer's Disease Neuroimaging Initiative, the National Alzheimer's Coordinating Centre database, and the Open Access Series of Imaging Studies). Clinical and MRI data collected between 2004 and 2022 were analysed with consistent methods, controlling for confounding factors, and combined using mixed-effects models.FindingsOur fully-automated method for PVS assessment showed excellent inter-scanner reproducibility (intraclass correlation coefficients >0.8). Fewer PVS and larger PVS diameter at baseline predicted higher dementia risk and accelerated brain atrophy. Longitudinal trajectories of PVS markers differed significantly in participants without dementia who converted to dementia compared with non-converters. In simulated placebo-controlled trials for treatments targeting cognitive decline, screening out participants at low risk of dementia based on our PVS markers enhanced the power of the trial independently of Alzheimer's disease biomarkers.InterpretationThese robust cerebrovascular markers predict dementia risk and brain atrophy and may improve risk-stratification of patients, potentially reducing cost and increasing throughput of clinical trials to combat dementia.FundingUS National Institutes of Health.

Extensive neovascularization is a hallmark of glioblastoma (GBM). In addition to supplying oxygen and nutrients, vascular endothelial cells provide trophic support to GBM cells via paracrine signaling. Here we report that Endocan (ESM1), an endothelial-secreted proteoglycan, confers enhanced proliferative, migratory, and angiogenic properties to GBM cells and regulates their spatial identity. Mechanistically, Endocan exerts at least part of its functions via direct binding and activation of the PDGFRA receptor. Subsequent downstream signaling enhances chromatin accessibility of the Myc promoter and upregulates Myc expression inducing stable phenotypic changes in GBM cells. Furthermore, Endocan confers radioprotection on GBM cells in vitro and in vivo. Inhibition of Endocan-PDGFRA signaling with ponatinib increases survival in the Esm1 wild-type but not in the Esm1 knock-out mouse GBM model. Our findings identify Endocan and its downstream signaling axis as a potential target to subdue GBM recurrence and highlight the importance of vascular-tumor interactions for GBM development.

Background: We investigated whether plasma β-hydroxybutyrate levels, a genetic risk score for Alzheimer's disease, and their interaction are associated with incident Alzheimer's disease. Methods: Using data from the UK Biobank—a population-based cohort study of adults aged 40–69 years, we assessed associations between baseline plasma β-hydroxybutyrate level, genetic risk score for Alzheimer's disease, and incident Alzheimer's disease. Incident Alzheimer's disease data were collected through linked data from hospital admissions and death registries. Results: In total, 261,933 adults were included, 1978 of whom developed incident Alzheimer's disease. Plasma β-hydroxybutyrate concentrations were not independently associated with Alzheimer's disease incidence after adjusting for covariates, whereas a higher genetic predisposition was linked to increased Alzheimer's disease incidence. Interactions were observed between plasma β-hydroxybutyrate concentrations and genetic risk for Alzheimer's disease on Alzheimer's disease incidence (P < 0.001). Conclusions: Further studies are warranted to elucidate the impact of plasma β-hydroxybutyrate status on Alzheimer's disease incidence.

BackgroundApolipoprotein E ε4 (APOE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (LOAD). A recent case report identified a rare variant in APOE, APOE3-R136S (Christchurch), proposed to confer resistance to autosomal dominant Alzheimer's Disease (AD). However, it remains unclear whether and how this variant exerts its protective effects.MethodsWe introduced the R136S variant into mouse Apoe (ApoeCh) and investigated its effect on the development of AD-related pathology using the 5xFAD model of amyloidosis and the PS19 model of tauopathy. We used immunohistochemical and biochemical analysis along with single-cell spatial omics and bulk proteomics to explore the impact of the ApoeCh variant on AD pathological development and the brain's response to plaques and tau.ResultsIn 5xFAD mice, ApoeCh enhances a Disease-Associated Microglia (DAM) phenotype in microglia surrounding plaques, and reduces plaque load, dystrophic neurites, and plasma neurofilament light chain. By contrast, in PS19 mice, ApoeCh suppresses the microglial and astrocytic responses to tau-laden neurons and does not reduce tau accumulation or phosphorylation, but partially rescues tau-induced synaptic and myelin loss. We compared how microglia responses differ between the two mouse models to elucidate the distinct DAM signatures induced by ApoeCh. We identified upregulation of antigen presentation-related genes in the DAM response in a PS19 compared to a 5xFAD background, suggesting a differential response to amyloid versus tau pathology that is modulated by the presence of ApoeCh. Bulk proteomics show upregulated mitochondrial protein abundance with ApoeCh in 5xFAD mice, but reductions in mitochondrial and translation associated proteins in PS19 mice.ConclusionsThese findings highlight the ability of the ApoeCh variant to modulate microglial responses based on the type of pathology, enhancing DAM reactivity in amyloid models and dampening neuroinflammation to promote protection in tau models. This suggests that the Christchurch variant's protective effects likely involve multiple mechanisms, including changes in receptor binding and microglial programming.

Natural products are ligands and in vitro inhibitors of Alzheimers disease (AD) tau. Dihydromyricetin (DHM) bears chemical similarity to known natural product tau inhibitors. Despite having signature polyphenolic character, DHM is ostensibly hydrophobic owing to intermolecular hydrogen bonds that shield hydrophilic phenols. Our research shows DHM becomes ionized at near-neutral pH, allowing the formulation of salts with transformed solubility. The MicroED co-crystal structure with trolamine reveals DHM salts as metastable co-crystalline solids with unlocked hydrogen bonding and a thermodynamic bent to solubilize in water. All co-crystal formulations show better inhibitory activity against AD tau than the nonsalt form, with efficacies correlating to enhanced solubilities. In vitro and in vivo pharmacokinetic measures demonstrate that DHM co-crystals display enhanced absorption and distribution with altered rates of elimination, suggesting that co-crystal formulations could be strategically used to fine-tune delivery properties. These results underscore the role of structural chemistry in guiding the selection of solubilizing agents for chemical formulation. We propose DHM co-crystals are appropriate formulations for research as dietary supplements to promote healthy aging by combating protein misfolding, although central nervous system (CNS) delivery remains a major limitation. DHM may be a suitable backbone for medicinal chemistry and possible development of pharmaceuticals with enhanced CNS exposure.

In late February 2024, the New Mexico State Legislature closed the books on a relatively uneventful session. After successive years of record revenues and double-digit budget expansion, the legislature modestly reigned in spending increases to less than 7%. Legislators continued their recent trend of stashing some of the state’s massive surplus in newly created endowment funds, hoping to insulate the state from future economic downturns. The legislative action reflects a growing consensus that boom and bust budgeting does not provide for a stable, long-term financial future. Legislators still managed to approve a $10 billion dollar plus budget, set aside reserves upwards of 30%, and spend almost $1.4 billion in capital projects big and small. Though the 30-day session is short, lawmakers still found time to deal with some social issues (public safety, health care, education, and the environment) and some issues personal to the legislature. Though only 72 pieces of legislation passed, the legislature managed to reset the compass on New Mexico’s financial structure while tinkering with current social concerns.

Working memory is an important skill for school success, and it involves holding information in our memory while using it to solve complex problems. However, autistic children often have difficulties with working memory tasks. Also, kindergarteners on the autism spectrum tend to be less school-ready compared with their peers. In addition, children from disadvantaged backgrounds tend to struggle more with working memory and school readiness skills. All preschool-age children on the autism spectrum in the United States are entitled to pre-kindergarten (pre-K) education. However, it is unclear whether attending pre-K helps with childrens working memory development in the long run. This study tested whether attending pre-K benefits childrens working memory development in the long run. It also tested whether pre-K is especially helpful for autistic childrens working memory development. It was found that children who attended pre-K outperformed their peers who did not attend pre-K during the first 2 years of elementary school. However, after first grade, such benefits diminished. Importantly, autistic children who attended pre-K did not demonstrate advanced working memory immediately in kindergarten, but they started to outperform their autistic peers who did not attend pre-K during first grade to third grade. This finding highlights the importance of pre-K education for autistic children in particular. It is also important for educators and parents to understand autistic childrens unique learning paths that may be different from non-autistic children. This article discusses specific ways for educators to take full advantage of the long-lasting benefits of pre-K education in autistic childrens working memory development.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with no known cure, limited treatment options with minimal benefits, and significant unmet need for disease modifying therapies. AIMS: This study investigated memantines impact on ALS progression, with an additional focus on the effects of memantine on cognitive and behavioral changes associated with the disease. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted from December 2018 to September 2020. ALS patients were enrolled in-person and remotely across 13 sites in the United States. Participants were randomized to memantine (20 mg twice daily) or placebo in a 2:1 ratio and completed 36 weeks of treatment. The primary outcome of disease progression was assessed by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and blood was collected for biomarker analysis. RESULTS: Of the 99 participants enrolled in the study, 89 were randomized to memantine or placebo (ages 24-83 years, male-to-female ratio ~3:2). Fifty-two participants completed the study treatment with no significant differences in disease progression, biomarker changes (including neurofilament light chain [NfL]), or neuropsychiatric testing noted between the groups. Initial NfL values correlated with the rate of ALSFRS-R decline. DISCUSSION: In this study, memantine did not impact ALS disease progression or neuropsychiatric symptoms. Trials with remote enrollment may help trial participation and success.